Neuroblastoma (NB) continues to be a common cancer in the pediatric population with high morbidity and mortality in the advanced stages. Our laboratory is dedicated to find new molecular targets to improve the dismal survival associated with advanced disease. By searching a neuroblastoma cDNA library, a new gene was identified containing the signature motifs of the dual-specificity phosphatase (DSP) family. In particular, the protein sequence contains the mitogen-activated protein (MAPK) phosphatase (MKP) motif; therefore, we named the protein MKP-8. Like other members of the DSP family, MKP-8 is able to dephosphorylate both tyrosine and serine/threonine phosphopeptide substrates. In addition, MKP-8 was found to significantly inhibit both p38 MAPK activity and critical phosphorylation of p53. Many types of cancer have the ability to bypass these pro-apoptotic pathways to promote proliferation and invasion. In regards to neuroblastoma, MKP-8 is expressed in many neuroblastoma cell lines and significantly overexpressed in high risk, stage III and IV disease. The goal of this proposal is to further elucidate the role of MKP-8 in the p38 MAPK/p53 pathways and establish MKP-8 as a new oncogene in neuroblastoma.